2,4-Toluene diisocyanate

584-84-9

Hazard Summary-Created in April 1992; Revised in January 2000

2,4-Toluene diisocyanate is primarily used as a chemical intermediate
in the production of polyurenthane products. 2,4-Toluene diisocyanate
is extremely toxic from acute (short-term) and chronic (long-term) exposures.
Acute exposure to high levels of 2,4-toluene diisocyanate in humans, via
inhalation, results in severe irritation of the skin and eyes and affects
the respiratory, gastrointestinal, and central nervous systems (CNS).
Chronic inhalation exposure to 2,4-toluene diisocyanate in humans has
resulted in significant decreases in lung function in workers, an asthma-like
reaction characterized by wheezing, dyspnea, and bronchial constriction.
Animal studies have reported significantly increased incidences of tumors
of the pancreas, liver, and mammary glands from exposure to 2,4-toluene
diisocyanate via gavage (experimentally placing the chemical in the stomach).
The International Agency for Research on Cancer (IARC) has classified
2,4-toluene diisocyanate as a Group 2B, possible human carcinogen.

EPA has not established a Reference Concentration (RfC)
or a Reference Dose (RfD) for
2,4-toluene diisocyanate. However, EPA has established an RfC
of 0.00007 milligrams per cubic meter (mg/m3) for the mixture
of toluene 2,4- and 2,6-diisocyanate based on respiratory effects in
humans. The RfC is an estimate
(with uncertainty spanning perhaps an order of magnitude) of a continuous
inhalation exposure to the human population (including sensitive subgroups),
that is likely to be without appreciable risk of deleterious noncancer
effects during a lifetime. It is not a direct estimator of risk but
rather a reference point to gauge the potential effects. At exposures
increasingly greater than the RfC,
the potential for adverse health effects increases. Lifetime exposure
above the RfC does not imply
that an adverse health effect would necessarily occur. (11)

EPA has medium confidence in the study on which the RfC
was based. Although the study was prospective and used appropriate endpoints
and state-of-the-art methods in monitoring, the lack of exposure
characterization in the first 2 years and the unknown relationship of
peak exposures to lung function decline detract from clear identification
of the no-observed-adverse-effect level (NOAEL)
and lowest-observed-adverse-effect level (LOAEL);
medium confidence in the database because of limitations in monitoring
and analytical procedures in the majority of occupational studies cited
and the uncertainties associated with peak vs. time-weighted-average
(TWA) exposures as determinants
of toxicity and, in addition, developmental toxicity data from a second
species are lacking; and consequently medium confidence in the RfC.
(11)

Reproductive/Developmental Effects:

No information is available on the reproductive or developmental
effects of 2,4-toluene diisocyanate in humans.

No reproductive or developmental effects were observed in rats exposed
to a mixture of toluene 2,4- and 2,6-diisocyanate via inhalation (11).

Cancer Risk:

Information is not adequate to determine the carcinogenic effects
of 2,4-toluene diisocyanate in humans. Three epidemiology studies did
not find an increased occurrence of cancer among exposed workers.

Animal studies have reported significantly increased incidences of
tumors of the pancreas, liver, and mammary glands from exposure to 2,4-toluene
diisocyanate via gavage. Animal studies, via inhalation, did not
report an increased incidence of tumors. (1,6)

A study by the National Toxicology Program (NTP) on a mixture of
toluene 2,4- and 2,6-diisocyanate administered by gavage showed an increase
in tumors of subcutaneous tissues in male and female rats, the pancreas
in male rats, mammary gland and liver in female rats, and liver and
circulatory system in female mice. (12)

EPA has not classified 2,4-toluene diisocyanate for carcinogenicity.

IARC has classified 2,4-toluene diisocyanate as a Group 2B, possible
human carcinogen. (5)

Health Data from Inhalation Exposure

ACGIH STEL--American Conference of Governmental and Industrial
Hygienists' short-term exposure limit; 15-min time-weighted-average exposure
that should not be exceeded at any time during a workday even if the 8-h
time-weighted-average is within the threshold limit value. ACGIH TLV--ACGIH's threshold limit value expressed as a time-weighted
average; the concentration of a substance to which most workers can be
exposed without adverse effects. LC50 (Lethal Concentration50)--A calculated
concentration of a chemical in air to which exposure for a specific length
of time is expected to cause death in 50% of a defined experimental animal
population. NIOSH IDLH--National Institute of Occupational Safety and Health
immediately dangerous to life and health; NIOSH concentration representing
the maximum level of a pollutant from which an individual could escape
within 30 minutes without escape-impairing symptoms or irreversible health
effects. OSHA PEL ceiling--Occupational Safety and Health Administration's
permissible exposure limit ceiling value; the concentration of a substance
that should not be exceeded at any time.

The health and regulatory values cited in this factsheet were obtained
in December 1999.aHealth numbers are toxicological numbers
from animal testing or risk assessment values developed by EPA. bRegulatory numbers are values that have been
incorporated in Government regulations, while advisory numbers are nonregulatory
values provided by the Government or other groups as advice. OSHA numbers
are regulatory, whereas NIOSH and ACGIH numbers are advisory.

J.E. Amoore and E. Hautala. Odor as an aid to
chemical safety: Odor thresholds compared with threshold limit values
and volatilities for 214 industrial chemicals in air and water dilution.
Journal of Applied Toxicology, 3(6):272-290. 1983.

National Institute for Occupational Safety and
Health (NIOSH). Pocket
Guide to Chemical Hazards. U.S. Department of Health and Human
Services, Public Health Service, Centers for Disease Control and Prevention.
Cincinnati, OH. 1997.